The ultimate objective of this project is to develop rapid in vitro biocompatibility methods to evaluate oral degradation of dental restorative resins. This innovation in biocompatibility testing is important for two reasons. First, new dental resins have unknown stability in the oral environment and they contain reactive chemicals, therefore manifesting potential systemic as well as oral toxicity. Second, there has been little advancement in the evaluation of dental polymers through fast short-term methods that stimulate long-term influences of the oral environment. In this study, existing in vitro methods will be enhanced and key new ones developed to produce a new battery of fast but exposure-relevant biocompatibility tests. This battery will be evaluated against existing standard methods with a set of reference dental restorative polymers of known biocompatibility. The study has four main objectives: (a) Creation of in vitro enzymatic and bacterial reagents and delivery systems. These will be simulators of molecular degradation at oral restorative surfaces, designed to accelerate the breakdown of polymeric precursors and facilitate rapid estimation of the leaching of toxic compounds from the polymers. (b) Development of new in vitro tests based upon the adherence of human fibroblasts to dental adhesives and composites to gain knowledge of bonding and the behavior of the polymers with human cells. (c) Development of bacterial assays to evaluate the cariogenic and toxicity potentiating or inhibiting properties of the new polymer formulations. (d) Identification of weakness in sampling techniques when using dental polymers in vitro. This program consists of three phases. In phase I, the new biocompatibility tests will be optimized. In Phase II the new methods will be compared to the current in vitro and in vivo methods using reference materials. The in vitro test systems will be evaluated for their ability to influence the degradation of current dental resins. To confirm that the tests simulate degradation the resins will be seeded with known cytotoxic and mutagenic marker substances. During Phase III, new dental adhesives and composites with promising chemical and toxicological properties will be evaluated using the new in vitro methods.